Normal embryonic development depends on the abilities of the individual cells to become collectively organized and differentiate coordinately. For this, the diverse cells in the embryo must be able to recognize one another so as to associate selectively into tissue-forming groupings. Our working hypothesis is that cell-recognition and selective cell contact depend on interactions of specific molecular arrays of the cell membrane; perturbations in cell-recognition (due to genetic or environmental causes) may result in congenital malformations and aberrant differentiation. Our goal is to elucidate the biochemical-cellular nature of embryonic cell recognition. We have obtained from embryonic cell-surfaces tissue-specific macromolecules which cause aggregation of cells into tissues; we have characterized one of them as a glycoprotein. We now propose to purify and characterize such cell-aggregating factors from different embryonic tissues, using also newly developed methods. We will study (by embryologic, immunological, biochemical, autoradiographic and EM procedures) how these molecules mediate morphogenetic cell association, their cellular specificities, presence at different embryonic and post-embryonic stages, role in cell differentiation, and if they are altered when morphogenesis is defective. We will explore their relationships (functional and genetic) to other determinants of cell surfaces, especially those directed by the T-locus. The role of cell-membrane interactions in regulating selective gene expression will be further analyzed, using induction of glutamine synthetase in embryonic neural retina as the experimental system. Changes in cell membranes during differentiation will further be examined through biological-biochemical studies on lectin "receptors". Thus, by pursuing a multidirectional approach (cellular-molecular-genetic) to analysis of specific cell-membrane components, this program aims to elucidate the role of the embryonic cell-surface in cell recognition, replication and differentiation, in normal and aberrant development.